VegT activation of Sox17 at the midblastula transition alters the responseto nodal signals in the vegetal endoderm domain

In Xenopas, the prospective endoderm and mesoderm are localized to discrete , adjacent domains at the beginning of gastrulation, and this is made evide nt by the expression of Sox17 in vegetal blastomeres and Brachyury (Xbra) i n marginal blastomeres. Here, we examine the regulation of Sox17 alpha expr ession and the role of Sox17 alpha in establishing the vegetal endodermal g ene expression domain. Injection of specific inhibitors of VegT or Nodal re sulted in a loss of Sox17 alpha expression in the gastrula. However, the on set of Sox17 alpha expression at the midblastula transition was dependent o n VegT, but not on Nodal function, indicating that Sox17 alpha expression i s initiated by VegT and then maintained by Nodal signals. Consistent with t hese results, VegT, but not Xenopus Nodal-related-1 (Xnr1), can activate So x17 alpha expression at the midblastula stage in animal explants. In additi on, VegT activates Sox17 alpha in the presence of cycloheximide or a Nodal antagonist, suggesting that Sox17 alpha is an immediate-early target of Veg T in vegetal blastomeres. Given that Nodal signals are necessary and suffic ient for both mesodermal and endodermal gene expression, we propose that Ve gT activation of Sox17 alpha at the midblastula transition prevents mesoder mal gene expression in response to Nodal signals, thus establishing the veg etal endodermal gene expression domain. Supporting this idea, Sox17 alpha m isexpression in the marginal zone inhibits the expression of multiple mesod ermal genes. Furthermore, in animal explants, Sox17 alpha prevents the indu ction of Xbra and MyoD, but not Sox17 beta or Mixer, in response to Xnr1. T herefore, VegT activation of Sox17 alpha plays an important role in establi shing a region of endoderm-specific gene expression in vegetal blastomeres. (C) 2001 Academic Press.